Klinefelter syndrome and mediastinal germ cell tumors

Völkl, Thomas M.K.; Langer, Thorsten; Aigner, Thomas; Greeß, H.; Beck, J. D.; Rauch, Anita; Dörr, Helmuth G.

doi:10.1002/ajmg.a.31103

Cited by 78 publications

(47 citation statements)

References 63 publications

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“…Germinomas are the most common of the GCTs, followed by mixed GCTs and teratomas. Interestingly, both mediastinal and intracranial GCTs may be associated with Klinefelter syndrome (47XYY), particularly when children present with precocious puberty [6,7]. There are regional differences in the incidence of GCTs.…”

Section: Overview: Pineal Region Tumor Types Germ Cell Tumorsmentioning

confidence: 97%

Management of pineal region tumors

Blakeley

Grossman²

2006

Curr. Treat. Options in Oncol.

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Tumors of the pineal region represent a diverse collection of tumors with a variety of natural histories. This diversity necessitates accurate histologic diagnosis to allow rational therapeutic planning. Evaluation of a pineal lesion should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF). Whereas certainty of the histologic diagnosis is now a requirement for treatment in Western nations, some Asian centers continue to recommend a test dose of radiation therapy based on the high incidence of germinoma in those countries. If there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or endoscopic biopsy may be pursued. All other lesions should be referred for open biopsy with microsurgical techniques. This approach provides adequate tissue for diagnosis, may be curative in low-grade tumors, and may substantially improve survival in patients with malignant tumors. If open surgery is not desired by the patient or practitioner, stereotactic or endoscopic biopsy may be followed by radiosurgery for localized, well-demarcated tumors. Radiation therapy is the first-line therapy for germinomas. Although the optimal radiation dosage and volume have not been decided, the current Children's Oncology Group trial may offer definitive evidence to address this dilemma in germ cell tumors. Evidence of CSF seeding requires craniospinal radiation and adjuvant chemotherapy regardless of tumor type. Diagnosis of any of the malignant tumors (non-germ cell tumors, pineoblastomas, and parenchymal tumors of intermediate determination) also requires craniospinal radiation (with local tumor doses of at least 50 Gy) and adjuvant chemotherapy (generally platinum based). Patients with tectal gliomas may undergo excision with or without postoperative radiation; however, they also may be observed with vigilant follow-up alone.

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Section: Overview: Pineal Region Tumor Types Germ Cell Tumorsmentioning

confidence: 97%

Management of pineal region tumors

Blakeley

Grossman²

2006

Curr. Treat. Options in Oncol.

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“…Interestingly, patients with Klinefelter syndrome (47,XXY) have no increased risk for testicular type-II GCTs, but they do for similar types of cancer of the mediastinal/thymus region. 48 This might be related to the fact that testicular germ cells disappear in XXY gonads, most likely because of an improper microenvironment. 49 The same may apply for the gonads of patients with complete androgen insensitivity.…”

Section: The Role Of Oct3/4 and The Y Chromosome In Type-ii Gctsmentioning

confidence: 99%

Tumor risk in disorders of sex development (DSD)

Looijenga¹,

Hersmus²,

Oosterhuis

et al. 2007

Best Practice & Research Clinical Endocrinology & Metab

195

139

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Disorders of sex development (DSD), previously referred to as intersex disorders, comprise a variety of anomalies defined by congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. Besides issues such as gender assignment, clinical and diagnostic evaluation, surgical and psychosocial management, and sex steroid replacement, the significantly increased risk for developing specific types of malignancies is both clinically and biologically relevant. This relates to germ-cell tumors specifically in DSD patients with hypovirilization or gonadal dysgenesis. The presence of a well-defined part of the Y chromosome (known as the GBY region) is a prerequisite for malignant transformation, for which the testis-specific protein on the Y chromosome (TSPY ) is a likely candidate gene. The precursor lesions of these cancers are carcinoma in situ (CIS)/intratubular germ-cell neoplasia unclassified (ITGCNU) in testicular tissue and gonadoblastoma in those without obvious testicular differentiation. Most recently, undifferentiated gonadal tissue (UGT) has been identified as the likely precursor for gonadoblastoma. The availability of markers for the different developmental stages of germ cells allows detailed investigation of the characteristics of normal and (pre)malignant germ cells. Although informative in a diagnostic setting for adult male patients, these markers -such as OCT3/4 -cannot easily distinguish (pre)malignant germ cells from germ cells showing delayed maturation. This latter phenomenon is frequently found in gonads of DSD patients, and may be related to the risk of malignant transformation. Thus, the mere application of these markers might result in over-diagnosis and unnecessary gonadectomy. It is proposed that morphological and histological evaluation of gonadal tissue, in combination with OCT3/4 and TSPY double immunohistochemistry and clinical parameters, is most informative in estimating the risk for germ-cell tumor development in the individual patient, and might in future be used to develop a decision tree for optimal management of patients with DSD.

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“…It is believed that the sex chromosomal aneuploidy in these men leads to early apoptosis of germ cells due to the inability for proper chromosome pairing during meiosis [Wikströ m et al, 2004]. However, men with Klinefelter syndrome have a higher risk of developing a highly aggressive GCC of the mediastinum and brain [Bokemeyer et al, 2002;Völkl et al, 2006;Queipo et al, 2008].…”

Section: Klinefelter As a Separate Groupmentioning

confidence: 99%

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

Spoor

Oosterhuis²,

Hersmus³

et al. 2017

Sex Dev

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Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a ‘genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research.

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Klinefelter syndrome and mediastinal germ cell tumors

Cited by 78 publications

References 63 publications

Management of pineal region tumors

Management of pineal region tumors

Tumor risk in disorders of sex development (DSD)

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

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